Naldi Marina, Baldassarre Maurizio, Domenicali Marco, Giannone Ferdinando Antonino, Bossi Matteo, Montomoli Jonathan, Sandahl Thomas Damgaard, Glavind Emilie, Vilstrup Hendrik, Caraceni Paolo, Bertucci Carlo
Department of Pharmacy and Biotechnology, Via Sand Donato 15, 40127, University of Bologna, Italy; Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
Center for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy; Department of Medical and Surgical Sciences, Via Massarenti 9, 40138, University of Bologna, Italy.
J Pharm Biomed Anal. 2016 Apr 15;122:141-7. doi: 10.1016/j.jpba.2016.01.048. Epub 2016 Jan 25.
Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before.
人血清白蛋白（HSA）是血浆中含量最丰富的蛋白质，具有多种与其胶体渗透压无关的生物学特性，如抗氧化和清除自由基活性、多种内源性和外源性物质的结合与转运，以及对内皮功能和炎症反应的调节。这些非胶体渗透压活性与白蛋白分子独特的动态结构密切相关。HSA会发生自发的结构修饰，主要是通过与氧化剂和糖类反应；然而，肝硬化患者的HSA在多个分子位点出现广泛的转录后变化，其程度与疾病的严重程度平行。本研究报告了一种创新的液相色谱 - 质谱分析方法的开发与应用，该方法可快速、可重复地测定酒精性肝炎（AH）患者血浆样本中HSA异构体的相对丰度。与AH患者中观察到的类似的严重氧化应激状态与循环HSA微异质性的深刻变化有关。更有趣的是，该分析平台提供的高分辨率使得能够监测以前从未报道过的HSA新氧化产物。
